The principal objective of the program of research outlined herein is the development of general strategies and methods for the synthesis of complex natural products possessing cytotoxic, cocarcinogenic, and antileukemic activities. The development of concise ways to approach these diverse classes of compounds is required to permit systematic structural variation for testing structure-activity relationships and for acquiring new compounds for biological evaluation as clinical candidates. During the course of these studies, it will be necessary to extend the scope and limitations of select known reactions in utilitarian ways and to invent new ones. The synthetic approaches are designed to be adequately flexible and efficient so as to allow for all the intended applications. The targeted compounds are primarily comprised of medium-sized and/or strained ring systems. For example, the strained In,out-bicyclo[4.4.1]undecan-4-one substructure of ingenol is hopefully to be accessed by tandem [3.3] sigmatropy and WagnerMeerwein rearrangement. Seco-ent-kaurenes such as shikodomedin are to be constructed by applicability of methodology developed in a model study in which five of the six requisite steps are 100% stereocontrolled. The taxanes, members of which possess potent antitumor activity, are to be approached by a new strategy involving an anionic oxy-Cope rearrangement step followed by 1,2-shift of the gem-dimethyl substituted bridge. A totally new approach to the construction of oxygen-bridged sesquiterpenes such as zexbrevin is expected to facilitate rapid assembly of these complex molecules. Success in this area will allow for extension of our goals to the preparation of piptocarphin A and related oxagermacranolides. Our quest of the antileukemic agent jatrophatrione is to take the form of an incredibly short sequence based on anionic [3.3] sigmatropy. Synthetic entry to the highly oxygenated antitumor agents neoliacinic acid and pseudopterolide and their analogues shall rely on several interesting techniques for establishing their manifold stereogenic centers.